PD-1阻断的免疫化疗已被确立为当前 mGEA 患者的标准一线治疗。回顾临床试验的历史，为 mGEA 免疫肿瘤学的演变提供了宝贵的见解，为该领域的未来发展铺平了道路。这篇综述总结了之前与转移性和局部晚期 GEA 患者免疫治疗相关的临床试验的结果我们还介绍了正在进行的临床试验，以解决当前临床实践中的挑战性问题。一般来说，GEA 表现出具有异质表达的中间免疫原性特征，抗 PD-(L)1 治疗的反应者大多富集于具有特定基因组的患者MSI-H、高 PD-L1 表达、高 TMB 和 EBV 相关类型等特征。正在探索与抗血管生成药物联合给药或同时阻断免疫检查点分子，以便为更多患者提供免疫治疗的益处。我们希望 CLDN18.2 和即将推出的 FGFR2b 等靶点能够补充 mGEA 领域免疫疗法的治疗利基。双特异性抗体、抗体药物偶联物、CAR-T和疫苗有望增强疗效并扩大免疫治疗的范围。

Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field.This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting, We also introduce ongoing clinical trials to address the current challenging issues in clinical practice.In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type. Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients. We hope that CLDN18.2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.